CD161(+)CD4(+) T cells are enriched in the liver during chronic hepatitis and associated with co-secretion of IL-22 and IFN-γ
| Autor: | Yu-Hoi Kang, C Willberg, Paul Klenerman, Eva Billerbeck, Vicki M. Fleming, Lucy J. Walker, Eleanor Barnes, David H. Adams, Bianca Seigel, Ruth Simmons, Bertram Bengsch, Anisha Bhagwanani, Ye Htun Oo, Hubert E. Blum, Robert Thimme |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
Hepatitis C virus Lymphocyte Immunology medicine.disease_cause Interleukin 22 03 medical and health sciences Interleukin 21 CD4+ T cell 0302 clinical medicine IL-22 Medicine Cytotoxic T cell Immunology and Allergy Original Research Article 030304 developmental biology 0303 health sciences hepatic inflammation business.industry interleukin-22 Interleukin-17 Hepatitis C medicine.disease CD4+ T cells 3. Good health medicine.anatomical_structure Liver HCV Interleukin 17 business lcsh:RC581-607 CD8 030215 immunology CD161 |
| Zdroj: | Frontiers in Immunology, Vol 3 (2012) Frontiers in Immunology |
| DOI: | 10.3389/fimmu.2012.00346 |
| Popis: | Hepatitis C virus infection is a major cause of chronic liver disease. CD4(+) T cells play a key role in disease outcome. However, the critical functions and associated phenotypes of intrahepatic CD4(+) T cells are not well defined. We have previously shown that CD8(+) T cells expressing the C type lectin CD161 are highly enriched in the human liver, especially during chronic hepatitis. These cells are associated with a type 17 differentiation pattern and express cytokines including IL-17A, IL-22, and IFN-γ. We therefore analyzed expression of CD161 on CD4(+) T cells in blood and liver and addressed the relevant phenotype and functional capacity of these populations. We observed marked enrichment of CD161(+)CD4(+) T cells in the liver during chronic hepatitis such that they are the dominant subtype (mean 55% of CD4(+) T cells). IL-22 and IL-17 secreting CD4(+) T cells were readily found in the livers of HCV(+) and NASH donors, although not enriched compared to blood. There was, however, specific enrichment of a novel subset of IL-22/IFN-γ dual secretors (p = 0.02) compared to blood, a result reconfirmed with direct ex vivo analyses. These data indicate the dominance of CD161(+) expressing lymphocyte populations within the hepatic infiltrate, associated with a distinct cytokine profile. Given their documented roles as antiviral and hepatoprotective cytokines respectively, the impact of co-secretion of IFN-γ and IL-22 in the liver may be particularly significant. |
| Databáze: | OpenAIRE |
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